Center for Reproductive Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, China.
J Clin Endocrinol Metab. 2018 Jul 1;103(7):2457-2467. doi: 10.1210/jc.2017-02459.
Endometrial insulin resistance (IR) may account for the endometrial dysfunction in polycystic ovary syndrome (PCOS). The underlying mechanism remains to be elucidated.
To investigate whether the abundance of 11β-hydroxysteroid dehydrogenases (11β-HSDs) 1 and 2 and cortisol as well as the insulin signaling pathway are altered in PCOS endometrium and to clarify the relationship between endometrial IR and local cortisol.
We measured cortisol and cortisone concentrations, 11β-HSD1 and 11β-HSD2, and core insulin signaling molecules in endometrial biopsies collected from non-PCOS and PCOS with or without IR patients on the seventh day after human chorionic gonadotropin injection. We also studied the effects of cortisol on glucose uptake and the insulin signaling pathway in primary cultured endometrial epithelial cells (EECs).
The cortisol concentration was elevated, whereas 11β-HSD2 expression was diminished in endometrial biopsies obtained from PCOS with IR patients compared with those from non-PCOS and PCOS without IR patients. The implantation rate was relatively impaired and the endometrial insulin signaling pathway was defective in PCOS with IR patients. In addition, cortisol attenuated insulin-stimulated glucose uptake in EECs, which was mediated by inhibition of Akt phosphorylation and glucose transporter type 4 translocation via induction of phosphatase and tensin homolog deleted on chromosome ten (PTEN).
Decreased oxidation of cortisol and defects of insulin signaling in endometrium were observed in PCOS with IR patients. The excessive cortisol level, derived from the reduction of 11β-HSD2, might contribute to the development of endometrial IR by inhibiting the insulin signaling pathway via induction of PTEN expression in EECs.
子宫内膜胰岛素抵抗（IR）可能是多囊卵巢综合征（PCOS）子宫内膜功能障碍的原因。其潜在机制仍有待阐明。
研究 11β-羟类固醇脱氢酶（11β-HSDs）1 和 2 以及皮质醇的丰度以及胰岛素信号通路是否在 PCOS 子宫内膜中发生改变，并阐明子宫内膜 IR 与局部皮质醇之间的关系。
我们测量了人绒毛膜促性腺激素注射后第 7 天取自非 PCOS 和 PCOS 伴或不伴 IR 患者的子宫内膜活检中的皮质醇和皮质酮浓度、11β-HSD1 和 11β-HSD2 以及核心胰岛素信号分子。我们还研究了皮质醇对原代培养的子宫内膜上皮细胞（EECs）葡萄糖摄取和胰岛素信号通路的影响。
与非 PCOS 和 PCOS 不伴 IR 患者相比，PCOS 伴 IR 患者的子宫内膜活检中皮质醇浓度升高，而 11β-HSD2 表达减少。IR 患者的种植率相对受损，子宫内膜胰岛素信号通路缺陷。此外，皮质醇通过抑制 Akt 磷酸化和葡萄糖转运蛋白 4（GLUT4）易位来减弱胰岛素刺激的 EECs 葡萄糖摄取，这是通过诱导第十号染色体缺失的磷酸酶和张力蛋白同源物（PTEN）介导的。
在 PCOS 伴 IR 患者中观察到子宫内膜中皮质醇的氧化减少和胰岛素信号转导缺陷。来源于 11β-HSD2 减少的皮质醇水平过高，可能通过诱导 EECs 中 PTEN 表达来抑制胰岛素信号通路，从而导致子宫内膜 IR 的发生。
